We propose to investigate in the living rat the mechanism(s) responsible for uptake of selected heavy metals from the perfused lumen of the jejunum, and for the accumulation of these metals in the jejunal mucosa or their further transport into the body. The metals of interest include Pb, Cd, Zn, Hg, Cu, and Ni. In each case we wish to determine whether separate, specific carrier systems are responsible for the transport of these metals: the observation that absorption of some metals is under homeostatic control, while no such control has been reported for others, suggests that only portions of the overall absorption mechanism may represent common pathways. Metal-metal interaction, and specificity of transport inhibitors will be measured. The role of intracellular ligands, such as metallothionein or sulfhydryl-containing compounds, on metal uptake and retention will be evaluated. Distribution of metals in the body will be compared after the same rate of either intestinal absorption or continuous intraperitoneal infusion by means of osmotic minipumps. This should permit some indication of the chemical form in which the metals are absorbed. The influence of dietary constituents and maturation of the intestine on metal absorption and distribution will also be studied.